Dr. Yuzhuo Wang, Ph.D. FCAHS (王玉琢院士) has a dual appointment as a Distinguished Scientist at the BC Cancer Research Centre and Senior Research Scientist at the Vancouver Prostate Centre. He is also the Founder of the Living Tumor Laboratory and a Professor in Department of Urologic Sciences at UBC. Dr. Wang did his Ph.D. at the University of Hong Kong, and joined Dr. Gerald R. Cunha at University of California, San Francisco (UCSF) as a postdoctoral fellow in 1997. Since then, He has authored/co-authored over 170 peer reviewed articles, many in top-tier journals such as Cancer Research, Cancer Cell, Cancer Discovery, Nature Medicine, Nature, Nature Communications, Clinical Cancer Research, and European Urology. He has published 13 book chapters and edited two books (i.e. PDX Model of Human Cancers and Tumor Dormancy). As a principal investigator, he is well funded by a number of agencies (e.g., the Canadian Institutes of Health Research).

Dr. Wang’s academic contributions can be highlighted by a number of novel hypotheses he has proposed, such as hypotheses on “prostate stem cells”, “epithelial-immune cell transition (EIT)”, “cancer-generated lactic acid is critical, immunosuppressive metabolite rather than a ‘waste product’ (which has been believed for more than 90 years)” and “tumour dormancy is a non-genetic disease”. Dr. Wang is recognized for his pioneering work in the field of prostate cancer modeling. He was the first to establish tissue recombination model of hormonal prostatic carcinogenesis. He also developed the first model of hormonal carcinogenesis in human prostatic epithelium. Moreover, he is responsible for a novel method for establishing transplantable, patient-derived xenograft models that closely resemble patients’ malignancies. Using the methodology, his group has developed over 300 transplantable patient-derived xenograft models in the Living Tumor Laboratory. Importantly such “next generation” xenograft models have been effectively applied in a number of research areas, such as (i) preclinical drug efficacy studies in anti-cancer therapeutics development, (ii) discovery and validation of potential biomarkers and/or therapeutic targets, and (iii) evidence-based personalized cancer therapy.

Dr. Wang has received numerous awards for his academic achievements in cancer research, such as a Prostate Cancer Foundation Research Award (2007), the Translation Research Award from Roche (2009), an Overseas Chinese Scholars Award from the National Natural Science Foundation of China (2009), the Innovative Scholar Award from the International Cancer Alliance for Research and Education (ICARE), US (2010), an UBC Faculty of Medicine Distinguished Achievement Award (2011), an UBC Department of Urologic Sciences Outstanding Academic Performance Award (2013) and a Department of Urologic Sciences Research Teaching Excellence Award (2015), and an UBC Department of Urologic Sciences Outstanding Academic Performance Award (2017). Notably, he has been inducted as a Fellow of  the Canadian Academy of Health Sciences (FCAHS) (加拿大健康科学院院士) in 2018.

Affiliations

Distinguished Scientist, Department of Experimental Therapeutics, BC Cancer

Senior Scientist, Vancouver Prostate Centre

Professor, Department of Urologic Sciences, University of British Columbia

Leader, Living Tumor Laboratory

Credentials

Post Doctoral Fellow, Department of Anatomy, University of California, San Francisco, 1997-2000

Ph.D. (Medicine), Department of Anatomy, University of Hong Kong, 1993-1997

M.Sc. (Biology), Department of Biology, Nankai University, China, 1986-1989

B.Sc. (Biology), Department of Biology, Nankai University, China, 1982-1986

Projects

Stromal Gene Expression Predicts And May Drive Metastasis in Prostate Cancer

Men with low to intermediate risk prostate cancer (PCa) face vexing decisions regarding treatment. The tumour can remain indolent and will not impact the patient within his lifetime, or it can progress to become life threatening (metastatic tumour). A holy grail of PCa research is the identification of prognostic biomarkers, which are biological factors that are associated with the disease outcomes, that can be used to improve patient risk stratification at time of diagnosis and guide treatment decisions.

Application of antibody internalization domain to improve the efficacy and safety of Antibody Drug Conjugates

Recent revolution in anti-cancer therapy utilizes the antibody's power to target cancer cells with chemotoxins. This approach of conjugating toxin to antibody (ADC= antibody drug conjugates) with specific affinity to cancer cells have dramatically improved both the safety and efficacy of the treatment. The most notable recent success is Kadcyla which combines DM1 toxin with anti-HER2 antibody to treat breast cancer. A critical factor in developing a successful ADC is an antibody's ability to internalize itself once it binds to the target cancer cell's biomarkers (receptors).

Identification of HP1a as a key regulator and a novel therapeutic target for neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) is a currently incurable, lethal subtype of prostate cancer that can develop from the disease following prolonged hormonal therapy. Unfortunately, there are few treatment options available for NEPC and new therapeutic targets and more effective treatments are urgently needed to improve its management. A state-of-the-art pre-clinical model of NEPC, developed in our group, is giving us unprecedented levels of accuracy in monitoring how NEPC progresses.

Function and therapeutic potential of SUV420H2 in neuroendocrine prostate cancer

Treatment-resistant neuroendocrine prostate cancer (NEPC) is a currently incurable, lethal subtype of prostate cancer that usually develops following prolonged hormonal therapy. The only treatment option for NEPC is a highly toxic chemotherapy, which provides only limited survival benefits. Therefore, more effective treatments are urgently needed to improve the management of NEPC. Our current research goal is to understand how NEPC develops and progresses and pave the road to develop new therapy for the disease treatment.

Selected Publications

Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2006
Cutz, Jean-Claude, Guan, Jun, Bayani, Jane, Yoshimoto, Maisa, Xue, Hui, Sutcliffe, Margaret, English, John, Flint, Julia, LeRiche, Jean, Yee, John, Squire, Jeremy A, Gout, Peter W, Lam, Stephen, Wang, Yu-Zhuo

Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenosine phosphorylase, an exploitable tumor target.

Molecular cancer therapeutics, 2012
Collins, Colin C, Volik, Stanislav V, Lapuk, Anna V, Wang, Yuwei, Gout, Peter W, Wu, Chunxiao, Xue, Hui, Cheng, Hongwei, Haegert, Anne, Bell, Robert H, Brahmbhatt, Sonal, Anderson, Shawn, Fazli, Ladan, Hurtado-Coll, Antonio, Rubin, Mark A, Demichelis, Francesca, Beltran, Himisha, Hirst, Martin, Marra, Marco, Maher, Christopher A, Chinnaiyan, Arul M, Gleave, Martin, Bertino, Joseph R, Lubin, Martin, Wang, Yuzhuo

High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development.

Cancer research, 2014
Lin, Dong, Wyatt, Alexander W, Xue, Hui, Wang, Yuwei, Dong, Xin, Haegert, Anne, Wu, Rebecca, Brahmbhatt, Sonal, Mo, Fan, Jong, Lina, Bell, Robert H, Anderson, Shawn, Hurtado-Coll, Antonio, Fazli, Ladan, Sharma, Manju, Beltran, Himisha, Rubin, Mark, Cox, Michael, Gout, Peter W, Morris, James, Goldenberg, Larry, Volik, Stanislav V, Gleave, Martin E, Collins, Colin C, Wang, Yuzhuo

Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer.

Genome biology, 2014
Wyatt, Alexander W, Mo, Fan, Wang, Kendric, McConeghy, Brian, Brahmbhatt, Sonal, Jong, Lina, Mitchell, Devon M, Johnston, Rebecca L, Haegert, Anne, Li, Estelle, Liew, Janet, Yeung, Jake, Shrestha, Raunak, Lapuk, Anna V, McPherson, Andrew, Shukin, Robert, Bell, Robert H, Anderson, Shawn, Bishop, Jennifer, Hurtado-Coll, Antonio, Xiao, Hong, Chinnaiyan, Arul M, Mehra, Rohit, Lin, Dong, Wang, Yuzhuo, Fazli, Ladan, Gleave, Martin E, Volik, Stanislav V, Collins, Colin C

Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.

Nature, 2015
Eirew, Peter, Steif, Adi, Khattra, Jaswinder, Ha, Gavin, Yap, Damian, Farahani, Hossein, Gelmon, Karen, Chia, Stephen, Mar, Colin, Wan, Adrian, Laks, Emma, Biele, Justina, Shumansky, Karey, Rosner, Jamie, McPherson, Andrew, Nielsen, Cydney, Roth, Andrew J L, Lefebvre, Calvin, Bashashati, Ali, de Souza, Camila, Siu, Celia, Aniba, Radhouane, Brimhall, Jazmine, Oloumi, Arusha, Osako, Tomo, Bruna, Alejandra, Sandoval, Jose L, Algara, Teresa, Greenwood, Wendy, Leung, Kaston, Cheng, Hongwei, Xue, Hui, Wang, Yuzhuo, Lin, Dong, Mungall, Andrew J, Moore, Richard, Zhao, Yongjun, Lorette, Julie, Nguyen, Long, Huntsman, David, Eaves, Connie J, Hansen, Carl, Marra, Marco A, Caldas, Carlos, Shah, Sohrab P, Aparicio, Samuel

Generation 2.5 antisense oligonucleotides targeting the androgen receptor and its splice variants suppress enzalutamide-resistant prostate cancer cell growth.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015
Yamamoto, Yoshiaki, Loriot, Yohann, Beraldi, Eliana, Zhang, Fan, Wyatt, Alexander W, Al Nakouzi, Nader, Mo, Fan, Zhou, Tianyuan, Kim, Youngsoo, Monia, Brett P, MacLeod, A Robert, Fazli, Ladan, Wang, Yuzhuo, Collins, Colin C, Zoubeidi, Amina, Gleave, Martin

Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015
Azad, Arun A, Volik, Stanislav V, Wyatt, Alexander W, Haegert, Anne, Le Bihan, Stephane, Bell, Robert H, Anderson, Shawn A, McConeghy, Brian, Shukin, Robert, Bazov, Jenny, Youngren, Jack, Paris, Pamela, Thomas, George, Small, Eric J, Wang, Yuzhuo, Gleave, Martin E, Collins, Colin C, Chi, Kim N

The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer.

Cell reports, 2015
Akamatsu, Shusuke, Wyatt, Alexander W, Lin, Dong, Lysakowski, Summer, Zhang, Fan, Kim, Soojin, Tse, Charan, Wang, Kendric, Mo, Fan, Haegert, Anne, Brahmbhatt, Sonal, Bell, Robert, Adomat, Hans, Kawai, Yoshihisa, Xue, Hui, Dong, Xin, Fazli, Ladan, Tsai, Harrison, Lotan, Tamara L, Kossai, Myriam, Mosquera, Juan Miguel, Rubin, Mark A, Beltran, Himisha, Zoubeidi, Amina, Wang, Yuzhuo, Gleave, Martin E, Collins, Colin C

Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis.

Cancer cell, 2015
El-Naggar, Amal M, Veinotte, Chansey J, Cheng, Hongwei, Grunewald, Thomas G P, Negri, Gian Luca, Somasekharan, Syam Prakash, Corkery, Dale P, Tirode, Franck, Mathers, Joan, Khan, Debjit, Kyle, Alastair H, Baker, Jennifer H, LePard, Nancy E, McKinney, Steven, Hajee, Shamil, Bosiljcic, Momir, Leprivier, Gabriel, Tognon, Cristina E, Minchinton, Andrew I, Bennewith, Kevin L, Delattre, Olivier, Wang, Yuzhuo, Dellaire, Graham, Berman, Jason N, Sorensen, Poul H
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